The present invention relates to a method for producing 4-cyano-3-oxyobutanoate and a process for producing 4-cyano-3-hydroxybutanoate, which is a useful intermediate compound for the production of pharmaceuticals (for example, JP-A-5-331128).
There has been disclosed a method for producing Ethyl 4-cyano-3-oxobutanoate by reacting ethyl 4-bromo-3-oxobutanoate with sodium hydride and reacting the resulting mixture with a cyanide ion in J. Chem. Soc. Chem. Comm. p932-933 (1977).
However, this method was not always satisfactory in that it requires tedious procedures as described above.
According to the present invention, 4-cyano-3-oxobutanoate can be readily obtained in an industrially improved process, and 4-cyano-3-hydroxybutanoate can also be readily obtained from 4-cyano-3-oxobutanoate.
The present invention provides:
1. a process for producing 4-cyano-3-oxobutanoate of formula (1): 
xe2x80x83wherein R denotes a C1-C8 alkyl group, which comprises reacting a 4-halo-3-oxobutanoate compound of formula (2): 
wherein X and R are defined as described above, with an alkali metal cyanide in methanol;
2. 4-cyano-3-oxobutanoate of formula (1): 
wherein R denotes a C1-C8 alkyl group, with the proviso that R is not an ethyl group; and
3. a process for producing 4-cyano-3-hydroxybutanoate of formula (3): 
wherein R denotes a C1-C8 alkyl group, which comprises reacting 4-cyano-3-oxobutanoate of formula (1): 
with an enzyme capable of converting 4-cyano-3-oxobutanoate of formula (1) to 4-cyano-3-hydroxybutanoate of formula (3), which enzyme has:
a) an amino acid sequence represented by SEQ ID NO:1, or
b) an amino acid sequence wherein one to several amino acids in the amino acid sequence represented by SEQ ID NO:1 are deleted, substituted or added (the enzyme is referred to as xe2x80x9cthe present enzymexe2x80x9d hereinafter).